This application is for the support of a General Clinical Research Center (CRC), consisting of eight patient beds and a supporting core laboratory, diet kitchen and outpatient examining rooms that will permit a wide variety of clinical investigations to be undertaken on patients of all ages. It will be made available to all departments of the School of Medicine, with collaborative efforts, in some cases, from individuals in the basic science division of our Graduate School. The objective will be to permit the direct application to clinical problems of the relevant basic information now being generated from research programs not only in the medical school, but throughout the University as well, with a minimum of delay. The CRC will thus serve to focus the efforts of many investigators on the intensive study of a wide spectrum of human diseases. The unusual strength of this school in biochemistry and genetics will in this manner be applied to human abnormalities of metabolism found in such widely divergent clinical disorders as cardiovascular disease, arthritis, diabetes, liver dysfunction, mental retardation, neurological disease, immunological disorders, renal dysfunction, endocrinology, hematology, as well as aberrations in various physiological functions, including those of cardiac physiology and reproduction. This unit will provide the missing segment needed to allow the smooth transmission of information in two different directions for the ultimate benefit of medical sciences. It will permit the dissection of clinical diseases into their more proximal causes leading eventually in some cases to explanations of the cellular, molecular, and basic genetic level. In the reverse direction, it will allow the synthesis of new and rational approaches to the correction of these clinical problems that are first tested at the basic molecular and cellular level then, through the CRC, evaluated in the patient with the disease. In addition, the Center will provide a vital interface with established research programs such as the Program Project on Human Biochemical Genetics of NIGMS, now established at this school, to permit the detailed study in depth of "nature's experiments" presented in the human inborn errors of metabolism.